AIDS-associated vacuolar myelopathy (VM) is a common neurologic complication of AIDS. Pathologically, VM is characterized by vacuolization in the lateral and posterior columns of the thoracic spinal cord and has a striking similarity with the myelopathy of vitamin B12 deficiency. In autopsy series, 20% to 55% of patients with AIDS have evidence of spinal cord disease consistent with VM. The myelopathy usually manifests late in the course of HIV infection, with slowly progressive weakness of the lower extremities, gait disorder, sensory abnormalities in the legs, impotence in men, and urinary frequency and urgency. Its course is invariably progressive and leads to severe paralysis of the lower limbs, with loss of the ability to walk and of sphincter control. The differential diagnosis is extensive and includes metabolic, infective, and neoplastic spinal cord diseases. The diagnosis is based on the clinical observation and the exclusion of other causes of myelopathy via serologic, radiographic, and cerebrospinal fluid studies. The pathogenesis of VM is unknown. Attempts to detect HIV in the spinal cord have not yielded significant results, and there is no evidence of a relationship between the presence of HIV and the development of myelopathy. A metabolic disorder of the vitamin B12-dependent transmethylation pathway, induced by HIV or cytokine activation, is considered the possible cause of VM associated with AIDS. There is no known treatment for AIDS myelopathy and there is no evidence that antiretroviral drugs can improve the symptoms or slow the progression of VM. The symptomatic treatment includes antispasticity agents, management of sphincter dysfunction, and physical therapy. Experimental treatments are being tested in clinical trials.